Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of disease conditions and has an increasing prevalence worldwide. A new review highlights how elevated uric acid (UA) may actively contribute to the development and progression of the disease. Evidence suggests that UA promotes inflammation, oxidative stress, and metabolic disturbances in the liver. It may serve as a biomarker and therapeutic target for improving MASLD diagnosis and treatment.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, has become one of the most common chronic liver conditions worldwide, affecting millions of people and placing increasing stress on global healthcare systems. The disease encompasses a spectrum ranging from mild steatosis to nonalcoholic steatohepatitis (NASH). While the early stages of the disease are associated with a lower mortality rate, survival declines dramatically in advanced stages. Also, the disease onset age often varies based on the region, necessitating the development of diagnostic tools and targeted treatment strategies. Despite its growing prevalence, due to its asymptomatic nature, MASLD risk identification and diagnosis are difficult. Given the complex pathophysiological mechanisms underlying the disease, new criteria are necessary to define MASLD more accurately.
Uric acid (UA) acts as a potent antioxidant under normal physiological conditions. However, high serum uric acid (SUA) level promotes inflammation, oxidative stress, and metabolic dysfunction and is closely linked to metabolic syndrome components, including insulin resistance, visceral obesity, and dyslipidemia. Elevated SUA level is also correlated with the severity of liver disease in patients with MASLD.
A new scientific review study by researchers from China, led by Dr. Weijing Zhang of Sun Yat-sen University Cancer Center, along with Dr. Xianzhi Liu and Dr. Tong Zhang of Xiamen University, China, highlights the emerging role of UA as a potential contributor to the development and progression of MASLD. “Elevated levels of UA may not simply be a consequence of metabolic disease but could actively influence liver damage and disease severity. We wanted to elucidate the roles of UA‐mediated epigenetic reprogramming, cellular crosstalk, and dysbiosis of the gut–liver axis in MASLD progression in our review study,” stated Dr. Zhang, while talking about the aim of the review. The study was published online in the Portal Hypertension & Cirrhosis journal on February 27, 2026.
Growing evidence suggests that hyperuricemia, elevated SUA level, is frequently observed in patients with MASLD. Studies have found that individuals with higher UA levels often show greater accumulation of fat in the liver and more severe histological signs of liver damage. Elevated UA has also been identified as an independent predictor of adverse outcomes, including progression to hepatocellular carcinoma and increased liver-related mortality.
Researchers propose several UA-associated molecular mechanisms that may contribute to MASLD development. One key pathway involves oxidative stress. Elevated UA can stimulate the production of reactive oxygen species, which damage liver cells and promote inflammation. The persistent oxidative stress may accelerate lipid accumulation, mitochondrial damage, and chronic inflammation in hepatocytes, worsening the liver injury.
UA also appears to influence inflammatory signaling in the liver. Increased UA levels can activate immune pathways that amplify inflammatory responses, further worsening liver damage. At the same time, uric acid may disrupt lipid metabolism and insulin signaling, two processes that play central roles in metabolic disorders and fatty liver disease.
Another emerging area of interest is the interaction between UA and the gut microbiome. Changes in gut microbial communities may influence UA metabolism and contribute to metabolic imbalance, potentially creating a feedback loop that accelerates disease progression.
The review also highlights potential therapeutic strategies targeting UA metabolism. Lifestyle interventions such as dietary changes and weight management can help reduce UA levels and improve metabolic health. In addition, medications that regulate UA production or enhance its excretion, currently used to treat hyperuricemia, are being explored as possible treatments for MASLD.
As UA interacts with multiple factors that are involved in MASLD, it is important to understand the etiology‐specific mechanism of UA involvement in the disease. Future research should also focus on the potential diagnostic value of UA and the development of biomarkers to improve diagnostic efficacy. As MASLD progression and characteristics differ due to individual variations, the efficacy and safety of UA-lowering drugs should be assessed carefully.
“Understanding the relationship between UA and liver metabolism could open new avenues for early diagnosis and treatment. By targeting metabolic pathways linked to uric acid, future therapies may help slow or prevent the progression of MASLD and reduce the burden of liver disease worldwide,” concluded Dr. Zhang.
About Xiamen University, China
Xiamen University (XMU), founded in 1921 is a public university in Siming, Xiamen, Fujian, China. It is affiliated with the Ministry of Education of China. XMU is recognized as one of China's leading universities and has been included in major government programs aimed at elevating selected universities to world-class status. The university is comprised of four campuses and is structured into six academic divisions, including 35 schools and colleges, as well as 17 research institutes. XMU is committed to develop the intellectual and personal strengths of its students and supports international collaborations.
Website: https://en.xmu.edu.cn/index.htm
About Sun Yat-sen University Cancer Center, China
Sun Yat-sen University Cancer Center (SYSUCC), established in 1964, is one of the four earliest tumor hospitals in China. It is one of the affiliated hospitals of the prestigious Sun Yat-sen University. It is the largest integrated cancer center in China for cancer care, education, research and prevention. SYSUCC’s mission is to help people prevent and cure cancer. SYSUCC closely combines its clinical and research attributes and to help bridge the gap between basic drug research and clinical applications, a Clinical Trial Center (CTC) was setup to assist physicians and scientists to test new therapies.
Website: https://english.sysucc.org.cn/index.aspx
About Dr. Xianzhi Liu and Dr. Tong Zhang from Xiamen University, China, and Dr. Weijing Zhang from Sun Yat-sen University Cancer Center, China
Dr. Tong Zhang is a part of the Department of General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, China. His expertise includes metabolomics, organ transplantation, liver disease, and cancer.
Dr. Xianzhi Liu belongs to the Department of Gastroenterology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, China. He has over 30 publications covering the fields such as liver disease, material science, and cancer.
Dr. Weijing Zhang is a part of the Department of Radiology at Sun Yat-sen University Cancer Center, China. He has published over 20 articles with expertise in biomedical engineering, material science, nanotechnology, and medical science.
Funding information
This work was supported by the Natural Science Foundation of Fujian Province (2024J01013), National Natural Science Foundation of China (82500759), Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (GZB20240394, 2025M772140), Xiamen Health High Quality Development Project (2024GZL-GG06), Foundation for Cultivated Young Talents of Fujian Province, China (2025350237), Fujian Provincial Health and Technology Program—Young and Middle-aged Key Talent Development Project (2025GGA095), and Young Investigator Research Program of Xiang'an Hospital of Xiamen University (XAH24007).
Portal Hypertension & Cirrhosis
Literature review
Not applicable
Uric Acid in Metabolic Dysfunction‐Associated Steatotic Liver Disease
27-Feb-2026
The authors declare no conflicts of interest